title: Different Na+/K+-ATPase signal pathways was involved in the increase of [Ca2+]i induced by strophanthidin in normal and failing isolated guinea pig ventricular myocytes.
abstract: OBJECTIVE
  To determine whether different Na+/K+-ATPase signal transduction pathways have positive inotropic effects on normal ventricular myocytes (NC) and failing ventricular myocytes (FC), and are involved in an increase of [Ca2+]i induced by strophanthidin (Str).
  
  
  METHODS
  A guinea pig model of congestive heart failure was made by constricting descending aorta. The left ventricular myocytes were enzymatically isolated. The effects of 25 micromol/L Str with different signal-transducing inhibitors on contractility and the calcium transient of NC or FC from guinea pigs were simultaneously assessed and compared with those in the 25 micromol/L Str-only group by a video-based, motion-edge detection system.
  
  
  RESULTS
  Str at 1, 10, and 25 micromol/L in NC and Str at 0.1, 1, 10, and 25 micromol/L) in FC elevated the calcium transient amplitude and increased the positive inotropic effects in a concentration-dependent manner, respectively. At the same concentration, the effects of Str were more potent in FC than in NC. In FC, both the mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) signal transduction pathway of Na+/K+-ATPase were involved in the increase of the calcium transient induced by Str, but only activation of the MAPK pathway increased the calcium transient in NC. However, only the ROS pathway was involved in positive inotropic effects both in NC and FC.
  
  
  CONCLUSIONS
  The present study suggests that Na+/K+-ATPase signaling pathways involved in the inotropic effects of Str in NC and FC are consistent, and Na+/K+-ATPase signaling pathways involved in the increase of [Ca2+]i by Str in NC and FC are different.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Ya-juan
authors.initials: YJ
authors.lastname: Qi
authors.forename: Su-wen
authors.initials: SW
authors.lastname: Su
authors.forename: Jun-xia
authors.initials: JX
authors.lastname: Li
authors.forename: Ji-he
authors.initials: JH
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Yong-li
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006168:Guinea Pigs; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D013327:Strophanthidin / Q000494:pharmacology*
chemical_list: D013327:Strophanthidin; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium